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Clinical Trials – Safety Reporting

1. Is Serious Adverse Event (SAE) report required to be submitted to NPRA?

SAE reporting is NOT required but SUSAR reporting to NPRAis mandatory.

In case of SAE reporting, the report should be submitted to the respective Ethics Committee depending on their requirements. We encourage you to check with the individual Ethics Committee to find out their reporting requirements.

2. What are the criteria for the reporting of Suspected Unexpected Serious Adverse Reaction (“SUSAR”) to NPRA?

The event must fulfil all the following criteria before reporting to NPRA:-
(a) The event is an adverse drug reaction (ADR). Please read FAQ # 3.
(b) The suspected drug is the investigational product, which requires CTIL/CTX, not the comparator or placebo.
(c) The ADR is serious. Please read FAQ # 4.
(d) The ADR is unexpected. Please read FAQ # 5.
(e) The source of report can be either local or overseas. In case of overseas report, it must come from the same clinical trial protocol as in Malaysia.
(f) The report must contain the minimum information for expedited reporting. Please read FAQ # 9.

3. What is Adverse Drug Reaction (ADR)?

In the pre-approval clinical experience with a new medicinal product or its new usages, all noxious and unintended responses to a medicinal product related to any dose should be considered as ADR. The phrase responses to a medicinal product means that a causal relationship between a medicinal product and an adverse event is at least a reasonable possibility, i.e. the relationship cannot be ruled out.

Regarding marketed medicinal products, ADR is a response to a drug which is noxious and unintended and which occurs at doses normally used in man for prophylaxis, diagnosis, or therapy of diseases or for modification of physiological function.

4. What is “Serious” Adverse Drug Reaction?

It is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability / incapacity, or is a congenital anomaly / birth defect.

Other important medical events that may not be immediately life-threatening or result in death or hospitalization, but when based on appropriate medical judgement, may jeopardise the subject or may require intervention to prevent of the outcomes in the definition of “Serious” ADR above should also be considered Serious ADR.

5. What is “Unexpected” Adverse Drug Reaction?

It is an adverse reaction where the nature or severity of which is not consistent with the application product information (e.g. Investigator’s Brochure for an unapproved investigational product or package insert / summary of product characteristics for an approved product).

6. Is SUSAR related to comparator or placebo NOT required for submission to NPRA?

YES.

7. When should we start and end SUSAR reporting for the clinical trial conducted in Malaysia?

SUSAR reporting should commence once CTIL/CTX has been approved for the trial in Malaysia. The reporting to NPRA ends when the CTIL/CTX has expired or the End of Study Summary Report has been submitted (within 3 months from site closure in Malaysia), whichever is later.

8. How to report SUSAR to NPRA?

9. What is the minimum information required for expedited reporting purposes?

The expedited report must include the following information, but not limited to:-
(a) An identifiable patient
(b) The name of a suspected medicinal product
(c) An identifiable reporting source
(d) An event or outcome that can be identified as serious and unexpected
(e) There is a reasonable suspected causal relationship

10. What should I do if I do not receive Acknowledgement of Receipt (AoR) for the submitted SUSAR reports which contain the minimum information?


You can verify the receipt of SUSAR reports by sending the following details on your submission as a query to the officers in charge. Please read the last FAQ for the officer in charge. Please be informed that phone call on this matter will not be entertained.
(a) The subject of email or SUSAR reference number
(b) Date of submission

11. What is the timeline for SUSAR reporting?

There are two (2) reporting timelines depending on the nature of report as following:-

(a) For SUSAR with death and/or life-threatening events, initial report should be submitted within 7 CALENDAR days and followed by full report as complete as possible within 8 additional CALENDAR days.

(b) For SUSAR with non fatal or non life-threatening events, initial report should be submitted within 15 CALENDAR days and followed by full report as it becomes available.

12. Is the timeline of SUSAR reporting counted from “Date Received by Manufacturer” or “Date of SUSAR Report” of a SUSAR report in CIOMS-I format?

The timeline starts from neither “Date Received by Manufacturer” nor “Date of SUSAR Report”. It starts after first knowledge by the sponsor that a case qualifies as a SUSAR for expedited reporting. This date should be written in the report.

13. Do we need to open/break the code (unblinding) prior to sending SUSAR reports to NPRA?

When a serious adverse reaction is judged reportable on an expedited basis, it is recommended that the blind be broken for that specific patient by the sponsor even if the investigator has not broken the blind. This is to prevent the placebo and comparator (usually a marketed product) cases to be filed unnecessarily.

When a fatal or other "serious" outcome is the primary efficacy endpoint in a clinical investigation, the integrity of the clinical investigation may be compromised if the blind is broken. Under these and similar circumstances, you should request from NPRA in advance to submit the blinded SUSAR reports or exempt from expedited reporting concerning serious events that would be treated as disease-related and not subjected to routine expedited reporting. When the blind is eventually opened, which may be many weeks or months after reporting to NPRA, an update in the CIOMS-I format as a follow up report will be sufficient.

14. Is it a MUST to report SUSAR in a secure mail?

NO.

15. Is there any requirement set forth by NPRA on SUSAR reporting to investigator?

NO. NPRA does not have any specific requirement on SUSAR reporting to Investigator. However, you should update the investigator adequately when the safety finding(s) could affect the safety of subjects, impact the conduct of the trial or alter the IRB/IEC's approval/favourable opinion to continue the trial.

16. In Malaysia, there are two clinical trials (Trial A and B) investigating the same drug/product. The CTIL/CTX holders for these two trials are from two different companies, i.e. Company C for Trial A and Company D for Trial B. If a SUSAR has arisen from Trial A, NPRA would like to receive this expedited report from company C only (as direct report) or both companies (additional cross report from company D)?

The party responsible for safety reporting should be clearly stated in the Clinical Trial Agreement (CTA). In most of the cases, Company C is responsible for safety reporting for Trial A whereas Company D for Trial B. Thus, in the above scenario, only Company C should expedite the SUSAR report to NPRA.

17. In Compassionate Use Programme, a named patient is given a privilege to have an early access to an unregistered product in Malaysia. Any SUSAR arisen from the programme should be reported to Centre for Investigational New Product or Centre for Post Registration?

(a) The programme is an extension of an approved clinical trial requiring CTIL and CTX and the named patient(s) is the subject who had previously enrolled in the trials.
SUSAR is reportable to Investigational Product Safety Monitoring Section, Centre for Investigation New Product.

(b) Once the products involved has successfully registered with DCA later.
SUSAR is reportable to Pharmacovigilance/ADR/MADRAC Unit, Centre for Post Registration. Please contact Head of Pharmacovigilance/ADR/MADRAC Unit, Ms. Noraisyah for more information on the reporting requirement via the email address Alamat emel ini dilindungi dari Spambot. Anda perlu hidupkan JavaScript untuk melihatnya.Alamat emel ini dilindungi dari Spambot. Anda perlu hidupkan JavaScript untuk melihatnya.">

18. Should the SUSAR arisen from the following named patient programme be reported to Centre for Investigational New Product or Centre for Post Registration?

(a) “Pengecualian untuk Mengimport / Mengilang Keluaran Tidak Berdaftar bagi Tujuan Merawat Penyakit yang Mengancam Nyawa”
(b) “Permohonan Memperolehi & Menggunakan Ubat yang Memerlukan Kelulusan Khas Ketua Pengarah Kesihatan Malaysia / Pengarah Kanan Perkhidmatan Farmasi”
SUSAR is reportable to Pharmacovigilance/ADR/MADRAC Unit, Centre for Post Registration. Please contact Head of Pharmacovigilance/ADR/MADRAC Unit, Ms. Noraisyah for more information on the reporting requirements via the email address Alamat emel ini dilindungi dari Spambot. Anda perlu hidupkan JavaScript untuk melihatnya.Alamat emel ini dilindungi dari Spambot. Anda perlu hidupkan JavaScript untuk melihatnya..">

19. Is it necessary to submit the following documents to NPRA?

(a) SUSAR Reports Line Listing
(b) Development Safety Update Report (DSUR)
(c) Annual Safety Report (ASR)
(d) Spontaneous Report

Currently, it is NOT compulsory to submit these documents to NPRA. However, voluntary submission of these documents at your discretion is accepted and encouraged. Since there is a limitation with our email reporting system on large file attachments, submission of these documents may be done in a CD with an accompanying cover letter. Kindly indicate the protocol number and itemise the content of the CD on the non-readable side of the CD.

20. Is there any guideline on safety reporting in clinical trial?

Kindly refer to the Malaysian Guideline for Safety Reporting of Investigational Products, 1st Edition, 2014 for more details. The guideline is available at Guidelines Central under the "Clinical Trials" tab.

21. Who should I refer to if I have any further queries on safety reporting in clinical trial?

Please direct your queries to our officers in charge via the following emails.

Mr. Nicholas Leow Chun Wei email: Alamat emel ini dilindungi dari Spambot. Anda perlu hidupkan JavaScript untuk melihatnya.
Mr. Wayne Wong Guan Wei email: Alamat emel ini dilindungi dari Spambot. Anda perlu hidupkan JavaScript untuk melihatnya.




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